The objectives of the proposed research are to increase understanding of the pathways by which vaccines induce immunity to tuberculosis and to utilize this knowledge as a basis for selecting vaccines and conditions of vaccination leading to increased acquired resistance accompanied by only transient tuberculin hypersensitivity. Vaccinated and nonvaccinated guinea pigs infected with two to four virulent tubercle bacilli by the respiratory route will be injected intravenously with in vitro or in vivo-grown streptomycin resistant tubercle bacilli or with placebo. At intervals after infection, individual lobes of the lungs, the bronchotracheal lymph nodes, spleen and liver will be removed and cultured on media with and without streptomycin. These experiments will be designed to discover (1) the events responsible for blocking hematogenous dissemination to the lung in BCG-vaccinated animals, (2) the relative contribution of tuberculin sensitivity and anamnestic response in tuberculoimmunity, and (3) to develop vaccines and vaccination regimens inducing increased protection accompanied by only transient tuberculin hypersensitivity.